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Research & Scholarship

Current Research and Scholarly Interests

Dr. Hammer's primary research interests are pediatric pharmacology and perioperative care of children undergoing cardiac surgery. He has numerous funded research projects in these areas, including an NIH grant for $4.3 million to study the pharmacology of sodium nitroprusside, a drug commonly used for blood pressure control in the operating room and ICU. Dr. Hammer has two other NIH grants and other ongoing research projects in the area of pediatric pharmacology.

Clinical Trials

Pharmacokinetics of Ketamine in Infants and ChildrenNot Recruiting

Dosing of medications is based on the plasma level achieved with a given dose and how long
the medicine remains in the body. This study is called pharmacokinetics-that is, what the
body does to the medication. Ketamine is an intravenous medication used for anesthesia and
sedation in children. However the pharmacokinetics of Ketamine has not been systematically
studied. We propose to study the pharmacokinetics of ketamine in different age groups of
children ranging from infants to teenagers.

Stanford is currently not accepting patients for this trial.For more information, please contact Archana Verma, (650) 721 - 1713.

Measuring the Amount of Methadone or Morphine in the Blood of Neonates, Infants & Children After Cardiac Surgery.Not Recruiting

Study Population:
Neonates, infants and children from birth to 5 years of age undergoing cardiac surgery with
CPB.
The use of methadone to provide analgesia may be increasing due to advantages compared to
other commonly used opioid analgesic drugs. While efficacy of methadone has been reported in
adults, there is a paucity of information in neonates and infants. In the latter population,
fentanyl and morphine are most commonly used for opioid analgesia following major surgery,
while methadone is frequently used for weaning of opioid dependent and tolerant patients, in
spite of the paucity of knowledge of methadone pharmacology in this population. There are
several clinical problems associated with fentanyl and morphine, and methadone may offer
superior efficacy with fewer side effects than these agents. We propose to study the
pharmacokinetics (PK) and pharmacodynamics (PD) of methadone in neonates and infants in the
intensive care unit following cardiac surgery.

Stanford is currently not accepting patients for this trial.For more information, please contact Gregory Hammer, (650) 723 - 7835.

An Open-label Study of Hydromorphone Oral Solution in Subjects Aged 28 Days to 16 Years for Postoperative PainRecruiting

The primary objective of this study is to characterize the pharmacokinetics and
pharmacodynamics of hydromorphone oral solution in pediatric subjects aged 28 days to 16
years inclusive. The secondary objectives are to characterize the safety and efficacy of
hydromorphone oral solution in pediatric subjects aged 28 days to 16 years inclusive.

Nitroprusside is used commonly in the Intensive Care Unit for long periods of time in order
to reduce blood pressure. It is not known if the body compensates over time to the blood
pressure lowering, and if when the nitroprusside is stopped the blood pressure goes up at a
faster rate and is higher than it was at the start of the treatment. This study will answer
these questions.

Dose-Response Study of Sodium Nitroprusside in Children Requiring Controlled Hypotension in the Operating RoomNot Recruiting

Sodium nitroprusside (SNP) has been approved for control of blood pressure in adults, yet
there are no controlled studies in children. The purpose of this study is to determine the
efficacy and safety of sodium nitroprusside in children who will be having surgery, and who
require blood pressure lowering in order to decrease the amount of blood loss during their
surgery.

The current literature in social epidemiology and public health suggests that low financial
savings has an unsurprising negative relationship with subjective well-being, and increases
the odds of making visits to a healthcare provider, receiving a chronic disease diagnosis,
and experiencing medical disability. Earn.org is a community-based non-profit based in San
Francisco with a mission to help low-income workers build lifelong savings habits and
financial capability. The organization is one of the largest providers of "goal-based savings
accounts" or "matched savings accounts" in the US. The investigators propose to conduct a
randomized controlled trial to determine the health effects of Earn's savings program.
Through this trial, the investigators will test three principal hypotheses: (1) Participants
in the Earn account, as compared to a control group, are hypothesized to demonstrate improved
scores on mental health scales assessing depression and anxiety.
(2) Participants in the Earn account, as compared to a control group, are hypothesized to
experience lower odds of harmful behaviors associated with stress, specifically tobacco and
alcohol abuse. The investigators hypothesize that the effect on behaviors will be of smaller
effect size, and more delayed, than the effect on mental health outcomes, judging from
similar effects observed in the micro-credit literature.
(3) The mediating variables between Earn account participation and beneficial health outcomes
will include increased optimism and internal locus of control.

Stanford is currently not accepting patients for this trial.For more information, please contact Sanjay Basu, (415) 881 - 7030.

Abstract

In the perioperative period, anesthesiologists and postanesthesia care unit (PACU) nurses routinely prepare and administer small-volume IV injections, yet the accuracy of delivered medication volumes in this setting has not been described. In this ex vivo study, we sought to characterize the degree to which small-volume injections (≤0.5 mL) deviated from the intended injection volumes among a group of pediatric anesthesiologists and pediatric postanesthesia care unit (PACU) nurses. We hypothesized that as the intended injection volumes decreased, the deviation from those intended injection volumes would increase.Ten attending pediatric anesthesiologists and 10 pediatric PACU nurses each performed a series of 10 injections into a simulated patient IV setup. Practitioners used separate 1-mL tuberculin syringes with removable 18-gauge needles (Becton-Dickinson & Company, Franklin Lakes, NJ) to aspirate 5 different volumes (0.025 mL, 0.05 mL, 0.1 mL, 0.25 mL, and 0.5 mL) of 0.25 mM Lucifer Yellow (LY) fluorescent dye constituted in saline (Sigma Aldrich, St. Louis, MO) from a rubber-stoppered vial. Each participant then injected the specified volume of LY fluorescent dye via a 3-way stopcock into IV tubing with free-flowing 0.9% sodium chloride (10 mL/min). The injected volume of LY fluorescent dye and 0.9% sodium chloride then drained into a collection vial for laboratory analysis. Microplate fluorescence wavelength detection (Infinite M1000; Tecan, Mannedorf, Switzerland) was used to measure the fluorescence of the collected fluid. Administered injection volumes were calculated based on the fluorescence of the collected fluid using a calibration curve of known LY volumes and associated fluorescence. To determine whether deviation of the administered volumes from the intended injection volumes increased at lower injection volumes, we compared the proportional injection volume error (loge [administered volume/intended volume]) for each of the 5 injection volumes using a linear regression model. Analysis of variance was used to determine whether the absolute log proportional error differed by the intended injection volume. Interindividual and intraindividual deviation from the intended injection volume was also characterized.As the intended injection volumes decreased, the absolute log proportional injection volume error increased (analysis of variance, P < .0018). The exploratory analysis revealed no significant difference in the standard deviations of the log proportional errors for injection volumes between physicians and pediatric PACU nurses; however, the difference in absolute bias was significantly higher for nurses with a 2-sided significance of P = .03.Clinically significant dose variation occurs when injecting volumes ≤0.5 mL. Administering small volumes of medications may result in unintended medication administration errors.

Abstract

The aim of this study was to characterize the relationship between morphine plasma concentration and repeated time to postoperative remedication events in children undergoing cardiac surgery.Data from our previously published study of morphine pharmacokinetics were utilized in this pharmacodynamic study. A population survival analysis based on hazard functions was undertaken in NONMEM(®).Hazard was best described by a Gompertz function changing in steps over time. Concentration and age were the only predictors of the hazard function. Concentration producing 50 % reduction in hazard was 19.6 (bootstrap 95 % confidence interval 5.90-49.5 ng/ml). The hazard ratio for a 1-year-old child to a 1-month-old child was 1.91 (1.35-2.86). Sensitivity to morphine decreased with age and leveled off after 1-year of life. Morphine sulfate doses >0.1 mg/kg did not noticeably increase tolerable pain durations.Time to remedication is a clinically useful endpoint for assessing opioid-induced analgesia. Sensitivity to morphine treatment is age-dependent. Morphine sulfate doses of 0.1-0.2 mg/kg are adequate for the management of postoperative pain in children. Our findings may help avoid unnecessary large morphine doses in children.

Abstract

Sodium nitroprusside is a direct-acting vasodilator used to lower blood pressure in the operating room and ICU. The efficacy of sodium nitroprusside has been analyzed in few pediatric randomized trials. This study assesses the efficacy and safety of sodium nitroprusside following at least 12 hours of IV infusion in children.Randomized, double-blind withdrawal to placebo study.ICUs.Pediatric patients younger than 17 years.Following 12-24 hours of open-label sodium nitroprusside titration, a blinded infusion of sodium nitroprusside or placebo was administered (at the stable rate used at the end of the open-label phase) for up to 30 minutes.The primary efficacy measure was whether control of mean arterial blood pressure was lost, that is, increased above ambient baseline for two consecutive minutes during the blinded phase. The proportion of patients who lost mean arterial blood pressure control in the placebo group (15/19; 79%) was significantly different than those in the sodium nitroprusside group (9/20; 45%) (p = 0.048). Three patients experienced rebound hypertension during the blinded phase, and all were in the placebo group. Serious adverse event rates were low (7/52; 13%), and in only one patient was the serious adverse event determined to be related to sodium nitroprusside by the site investigator. Fourteen patients (27%) had whole blood cyanide levels above 0.5 μg/mL, with high correlation (0.7) between infusion rate and cyanide levels, but there were few clinical signs of cyanide toxicity.Sodium nitroprusside is efficacious in maintaining mean arterial blood pressure control in children following a 12-hour infusion. Although a high proportion of patients were found to have elevated cyanide levels, toxicity was not observed.

Abstract

Etomidate is a rapid-onset, short-acting hypnotic medication administered for induction of anesthesia. It is currently approved by the Food and Drug Administration for use in older children and adults. Pharmacokinetic data to help guide dosing in neonates and infants is lacking.The aim of this study was to determine the pharmacokinetics of etomidate in neonates and infants with congenital heart disease undergoing cardiac surgery.Four neonates and sixteen infants, postnatal age 0.3 - 11.7 months, requiring open-heart surgery received 0.3 mg/kg of etomidate administered as a single intravenous dose prior to surgery. Blood sampling for plasma etomidate concentration occurred immediately following etomidate administration until the initiation of cardiopulmonary bypass. A population pharmacokinetic approach using nonlinear mixed-effects modeling was applied to characterize etomidate pharmacokinetics.The pharmacokinetics of etomidate was described by a two-compartment model with first-order elimination. An allometric weight-based model was applied to scale results to a 70 kg adult. Covariates including age and cardiac physiology were not found to significantly impact etomidate pharmacokinetics. The study population was found to have a central and intercompartmental clearance of 0.624 L/min/70-kg and 0.44 L/min/70-kg, respectively; central and peripheral distribution volume of 9.47 and 22.8 L/70-kg, respectively. Inter-individual variability was between 94-142% for all parameters and residual variability was 29%.The clearance of etomidate is lower in neonates and infants with congenital heart disease compared to published values for older children without congenital heart disease. In addition, etomidate pharmacokinetics is highly variable in this pediatric cardiac population. This article is protected by copyright. All rights reserved.

Abstract

This study aims at developing a population pharmacokinetic model for ketamine in children with cardiac diseases in order to rationalize an effective 2-h anesthetic medication, personalized based on cardiac function and age. Twenty-one children (6 months to 18 years old) were enrolled in this prospective, open label study. Ketamine 2mg/kg IV was administered and blood samples were then collected over 8h for ketamine assay. Pharmacokinetic data analysis using NONMEM, was undertaken. Ketamine pharmacokinetics was adequately described by a two-compartment linear disposition model. Typical population parameters were: total clearance: 60.6×(weight/70)(0.75)L/h, intercompartmental clearance: 73.2×(weight/70)(0.75)L/h, central distribution volume: 57.3×(weight/70)L, and peripheral distribution volume: 152×(weight/70)L. Ketamine clearance in children with pre-existing congenital heart disease was comparable to values reported in healthy subjects. Computer simulations indicated that an initial loading dose of ketamine 2mg/kg IV over 1min followed by a constant rate infusion of 6.3mg/kg/h for 29min, 4.5mg/kg/h from 30 to 80min, and 3.9mg/kg/h from 80 to 120min achieves and maintains anesthetic plasma level for 2h in children 1 year or older (weight ≥10kg).

Abstract

(1) To define the onset and offset of the blood-pressure-lowering effects of sodium nitroprusside (SNP) for use in developing instructions for dose titration in children undergoing a surgical or medical procedure, and (2) to assess the safety of SNP administration in pediatric patients requiring controlled reduction of blood pressure.We conducted a randomized, double-blind, parallel-group, dose-ranging, effect-controlled, multicenter study of intravenous (IV) infusions of SNP in pediatric patients <17 years, who required controlled hypotension for at least 2 h while undergoing a surgical or medical procedure. A blinded SNP dose of 0.3, 1, 2, or 3 μg/kg/min was infused for 30 min, followed by open-label administration for at least 90 min. Both infusions were titrated to effect.The final intent-to-treat group comprised 203 patients. Significant reductions in mean arterial pressure (MAP) from baseline were observed for all four doses at 20 and 25 min after the start of infusion (p ≤ 0.009 and p ≤ 0.010 for each time, respectively). Overall, 98.5% of the patients achieved the target MAP; 72.9% first achieved the target MAP during the blinded infusion. The mean infusion rate at target MAP was 1.07 μg/kg/min.We determined that 0.3 μg/kg/m is a reasonable starting dose for SNP in pediatric patients requiring controlled hypotension. The infusion rate can then be increased to achieve the desired reduction in blood pressure. On the basis of our results, we found an average infusion rate of 1 μg/kg/min might be appropriate. Of note, no cyanide toxicity was reported, and no measureable cyanide levels were detected in any blood samples obtained during the study. http://clinicaltrials.gov/show/NCT00135668.

Abstract

Sodium nitroprusside (SNP) has been widely used to control blood pressure in infants and children. The goals of this analysis were to develop models that describe the hemodynamic response to SNP dosing in pediatric patients; examine sources of variation in dose-response, defining age, and size dependencies; and determine vulnerable populations or patient subtypes that may elicit dosing modifications. A multi-center, randomized, double-blinded, parallel-group, dose-ranging, effect-controlled study, followed by an open-label dose titration of an intravenous infusion of SNP was undertaken in 203 pediatric subjects, who required deliberate hypotension or controlled normotension during anesthesia. A total of 3464 MAP measurements collected from 202 patients during the study's blinded phase, including baseline measurements up to 6 min prior to the blinded were available for analysis. A population K-PD model was developed with a one-compartment model assumed for SNP. Size differences in CL and V of the effect compartment were described using theory-based allometry. An inhibitory sigmoidal Emax model was used to describe the effect of SNP. A power function of age was used to describe age-related differences in baseline MAP. A mixture model of two groups with low and high EC50 was used to explain variability in MAP response. Change in MAP was characterized by a linear disease progression slope during the blinded phase. In the final population model, CL and V increased with weight, and baseline MAP increased with age. The effect compartment half-life of SNP was 13.4 min. The infusion rate producing 50% of Emax (ER50) at steady state for high EC50, was 0.34 μg/kg/min and for low EC50 0.103 μg/kg/min. The K-PD model well-describes initial dosing of SNP under controlled circumstances; model-based dosing guidance agrees with current practice. An initial titration strategy supported via algorithm-based feedback should improve maintenance of target MAP.

Abstract

Sodium nitroprusside (SNP) is used to decrease arterial blood pressure (BP) during certain surgical procedures. There are limited data regarding efficacy of BP control with SNP. There are no data on patient and clinician factors that affect BP control. We evaluated the dose-response relationship of SNP in infants and children undergoing major surgery and performed a quantitative assessment of BP control.One hundred fifty-three subjects at 7 sites received a blinded infusion followed by open-label SNP during operative procedures requiring controlled hypotension. SNP was administered by continuous infusion and titrated to maintain BP control (mean arterial BP [MAP] within ±10% of clinician-defined target). BP was recorded using an arterial catheter. Statistical process control methodology was used to quantify BP control. A multivariable model assessed the effects of patient and procedural factors.BP was controlled an average 45.4% (SD 23.9%; 95% CI, 41.5%-49.18%) of the time. Larger changes in infusion rate were associated with worse BP control (7.99% less control for 1 μg·kg·min increase in average titration size, P = 0.0009). A larger difference between a patient's baseline and target MAP predicted worse BP control (0.93% worse control per 1-mm Hg increase in MAP difference, P = 0.0013). Both effects persisted in multivariable models.SNP was effective in reducing BP. However, BP was within the target range less than half of the time. No clinician or patient factors were predictive of BP control, although 2 inverse relationships were identified. These relationships require additional study and may be best coupled with exposure-response modeling to propose improved dosing strategies when using SNP for controlled hypotension in the pediatric population.

Abstract

The lack of methadone pharmacokinetic data in children and neonates restrains dosing to achieve the target concentration in these populations. A minimum effective analgesic concentration of methadone in opioid naïve adults is 0.058 mg·l(-1) , while no withdrawal symptoms were observed in neonates suffering opioid withdrawal if plasma concentrations of methadone were above 0.06 mg·l(-1) . The racemate of methadone which is commonly used in pediatric and anesthetic care is metabolized to 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP).Data from four studies (age 33-week PMA-15 years) were pooled (n = 56) for compartment analysis using nonlinear mixed effects modeling. Parameter estimates were standardized to a 70-kg person using an allometric model approach. Investigation was made of the racemate and metabolite (EDDP and EMDP) dispositions. In addition, neonatal data (n = 7) allowed further study of R- and S-enantiomer pharmacokinetics.A three-compartment linear disposition model best described the observed time-concentration profiles with additional compartments for metabolites. Population parameter estimates (between-subject variability) were central volume (V1) 21.5 (29%) l.70 kg(-1) , peripheral volumes of distribution V2 75.1 (23%) l.70 kg(-1) and V3 484 (8%) l.70 kg(-1) , clearance (CL) 9.45 (11%) l·h(-1) .70 kg(-1) , and intercompartment clearances Q2 325 (21%) l·h(-1) .70 kg(-1) and Q3 136 (14%) l·h(-1) .70 kg(-1) . EDDP formation clearance was 9.1 (11%) l·h(-1) .70 kg(-1) , formation clearance of EMDP from EDDP 7.4 (63%) l·h(-1) .70 kg(-1) , elimination clearance of EDDP was 40.9 (26%) l·h(-1) .70 kg(-1) and the rate constant for intermediate compartments 2.17 (43%) h(-1) .Current pharmacokinetic parameter estimates in children and neonates are similar to those reported in adults. There was no clearance maturation with age. Neonatal enantiomer clearances were similar to those described in adults. A regimen of 0.2 mg·kg(-1) per 8 h in neonates achieves a target concentration of 0.06 mg·l(-1) within 36 h. Infusion, rather than intermittent dosing, should be considered if this target is to be achieved in older children after cardiac surgery.

Abstract

BACKGROUND: Dexmedetomidine is an alpha2-adrenergic agonist used for sedation and analgesia in children. We previously showed that dexmedetomidine depresses sinus and AV nodal function resulting in adverse hemodynamic effects such as bradycardia and increased blood pressure. We hypothesized that these effects of dexmedetomidine might be antagonized by co-administration of ketamine, which has sympathomimetic properties. METHODS: Twenty-two children (ages 5-17 years) undergoing electrophysiologic (EP) study and ablation for supraventricular tachycardia were enrolled. Patients were kept sedated with continuous infusion of propofol at a fixed rate. Hemodynamic and EP parameters were measured before and after a loading dose of dexmedetomidine (1 μg·kg(-1) ). A continuous infusion of dexmedetomidine (0.7 μg·kg(-1) ·h(-1) ) was initiated and a ketamine loading dose (1 mg·kg(-1) ), followed by continuous infusion (1 mg·kg(-1) ·h(-1) ), was given. A repeat set of hemodynamic and EP parameters were then measured at the time of projected peak tissue concentration for both drugs. RESULTS: A significant increase in mean arterial pressure (MAP) was seen compared with baseline after loading of dexmedetomidine. This returned to baseline after co-administration of ketamine (mean difference between baseline and after ketamine 1.8 mmHg; 95%CI, -7.8 to 4.3; P = <0.001). A decrease in heart rate was seen after dexmedetomidine followed by a return to baseline after co-administration of ketamine (mean difference between baseline and after ketamine -6.5 bpm; 95%CI, -11.2 to -1.8; P = 0.005). Sinus node recovery time was lengthened after dexmedetomidine but returned to baseline after ketamine (mean difference between baseline and after ketamine -16.2 ms; 95%CI, -63 to 30; P = 0.014). QT was prolonged after dexmedetomidine and returned to baseline after ketamine (mean difference between baseline and after ketamine -34.2 ms; 95%CI, -48.4 to -20.2; P = 0.004). AV nodal effective refractory period was also impaired after dexmedetomidine and showed weak evidence for return to baseline function after ketamine (mean difference between baseline and after ketamine -22.8 ms; 95%CI, -40.2 to -5.2; P = 0.069). CONCLUSION: The concurrent use of ketamine may mitigate the negative chronotropic effects of dexmedetomidine.

Abstract

Most hospital laboratories do not measure blood cyanide concentrations, and samples must be sent to reference laboratories. A simple method is needed for measuring cyanide in hospitals. The authors previously developed a method to quantify cyanide based on the high binding affinity of the vitamin B12 analog, cobinamide, for cyanide and a major spectral change observed for cyanide-bound cobinamide. This method is now validated in human blood, and the findings include a mean inter-assay accuracy of 99.1%, precision of 8.75% and a lower limit of quantification of 3.27 µM cyanide. The method was applied to blood samples from children treated with sodium nitroprusside and it yielded measurable results in 88 of 172 samples (51%), whereas the reference laboratory yielded results in only 19 samples (11%). In all 19 samples, the cobinamide-based method also yielded measurable results. The two methods showed reasonable agreement when analyzed by linear regression, but not when analyzed by a standard error of the estimate or paired t-test. Differences in results between the two methods may be because samples were assayed at different times on different sample types. The cobinamide-based method is applicable to human blood, and can be used in hospital laboratories and emergency rooms.

Abstract

Ketorolac tromethamine (ketorolac) administration reduces postoperative opioid requirements. The pharmacokinetic characteristics of intranasal ketorolac tromethamine in children have not been characterized. Our objective of this study was to determine the pharmacokinetics of a single intranasal dose of ketorolac in adolescent patients.Twenty surgical patients, ages 12 to 17 years, were enrolled. After surgery, subjects received intranasal ketorolac 15 mg (weight ≤50 kg) or 30 mg (weight >50 kg) using a proprietary administration system. Blood samples were obtained for ketorolac assay at baseline (within 15 minutes before the dose) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after the dose. A population analysis was undertaken using nonlinear mixed-effects models. Parameter estimates were standardized to a 70-kg person.The intranasal dosing in adolescents was well tolerated with minimal adverse effects. A 1-compartment model with first-order absorption and elimination was satisfactory to describe time-concentration profiles. Population parameter estimates (between subject variability) were clearance (CL/F) 2.05 L/h (60.5%), volume of distribution (V/F) 15.2 L (32.4%), absorption half-life (t(1/2)abs) 0.173 hour (25.0%). Time to peak concentration (Tmax) was 52 minutes (SD 6 minutes).Administration of ketorolac by the intranasal route resulted in a rapid increase in plasma concentration and may be a useful therapeutic alternative to IV injection in adolescents because plasma concentrations attained with the device are likely to be analgesic (investigational new drug no. 62,829).

Abstract

Cardiomyopathy is an important cause of heart failure and a major indication for heart transplantation in children. Unfortunately, there is a paucity of literature to guide the anesthesiologist who cares for these high-risk children. This review describes the cardiomyopathy phenotypes that occur in children and the factors that are associated with clinical outcomes and perioperative complications. Anesthesia considerations will be reviewed.During the past decade, there has been a dramatic increase in knowledge related to cardiomyopathy. New genotypes and phenotypes are recognized and new therapies have been devised. Multicenter pediatric cardiomyopathy registries are obtaining data essential for enhanced understanding of the disease.The diverse spectrum and complexity of pediatric cardiomyopathies mandate a thorough appreciation of the cardiac pathophysiology pertinent to an individual child's perioperative management. Important issues include multisystem disease associated with syndromic or genetic disorders, appropriate preoperative patient assessment to adequately characterize patient risk and guide therapy, and intraoperative and postoperative care plans that target optimal outcomes.

Abstract

The purpose of this article is to provide a brief but systematic overview of heart failure and cardiomyopathy in children and the anesthetic management of these patients. We will begin with disease definitions and descriptions of the disorders. Our review will include the epidemiology and etiology of the more prevalent underlying causes of heart failure, the principal pathophysiology of the specific cardiomyopathies, as well as the common therapies in use today in both inpatient and outpatient settings. Important implications for anesthetic management will be highlighted.

Abstract

Opioids such as morphine are the cornerstone of pain treatment. The challenge of measuring the concentrations of morphine and its active metabolites in order to assess human pharmacokinetics and monitor therapeutic drugs in children requires assays with high sensitivity in small blood volumes. We developed and validated a semi-automated LC-MS/MS assay for the simultaneous quantification of morphine and its active metabolites morphine 3β-glucuronide (M3G) and morphine 6β-glucuronide (M6G) in human plasma and in dried blood spots (DBS). Reconstitution in water (DBS only) and addition of a protein precipitation solution containing the internal standards were the only manual steps. Morphine and its metabolites were separated on a Kinetex 2.6-μm PFP analytical column using an acetonitrile/0.1% formic acid gradient. The analytes were detected in the positive multiple reaction mode. In plasma, the assay had the following performance characteristics: range of reliable response of 0.25-1000 ng/mL (r(2) > 0.99) for morphine, 1-1,000 ng/mL (r(2) > 0.99) for M3G, and 2.5-1,000 ng/mL for M6G. In DBS, the assay had a range of reliable response of 1-1,000 ng/mL (r(2) > 0.99) for morphine and M3G, and of 2.5-1,000 ng/mL for M6G. For inter-day accuracy and precision for morphine, M3G and M6G were within 15% of the nominal values in both plasma and DBS. There was no carryover, ion suppression, or matrix interferences. The assay fulfilled all predefined acceptance criteria, and its sensitivity using DBS samples was adequate for the measurement of pediatric pharmacokinetic samples using a small blood of only 20-50 μL.

Abstract

Dexmedetomidine is an α(2)-adrenoceptor agonist with sedative, anxiolytic and analgesic properties. It is used off-label in pediatric patients due to its efficacy and lack of adverse respiratory effects. Dexmedetomidine may cause severe circulatory complications in adults. Despite its popularity, the safety of dexmedetomidine in the pediatric population has not been extensively studied.This article reviews the current literature (up to 2010) focusing on applications and safety of dexmedetomidine administered to pediatric patients.Dexmedetomidine is a useful sedative and anxiolytic drug in the pediatric intensive care unit as well as during diagnostic and therapeutic procedures. Deleterious effects of dexmedetomidine include hypotension and bradycardia. Additionally, hypertension may occur during the "loading dose" or with high infusion rates. Few studies have been performed to evaluate the safety of dexmedetomidine in pediatrics. The development of tolerance and withdrawal has not been studied in children.Despite its favorable respiratory profile, dexmedetomidine may cause deleterious cardiovascular effects. Close monitoring of circulatory dynamics and judicious titration is recommended. Further studies are needed to better define adverse effects following long-term infusions as well as in special populations such as pre-term infants.

Abstract

We sought to characterize the airway responses to desflurane during maintenance of and emergence from anesthesia in children whose airways were supported with laryngeal mask airways (LMAs).Four hundred healthy children were randomized in a 3 : 1 ratio to either desflurane or isoflurane (reference group) during anesthetic maintenance. After induction of anesthesia, anesthesia was maintained with the designated anesthetic. The investigator chose the airway (LMA and facemask), ventilation strategy and when to remove the LMA. The incidence of airway events during maintenance, emergence and recovery was recorded.Ninety percent of children received LMAs. The frequency of major airway events after desflurane (9%) was similar to that after isoflurane (4%) (number needed to harm [NNH] 20), although the frequency of major events after the LMA was removed during deep desflurane anesthesia (15%) was greater than during awake removal (5%) (NNH 10) (P < 0.006) and during deep isoflurane removal (2%) (NNH 8) (P < 0.03). The frequency of airway events of any severity after desflurane was greater than that after isoflurane (39% vs 27%) (P < 0.05). The frequencies of laryngospasm and coughing of any severity after desflurane were greater than those after isoflurane (13% vs 5% and 26% vs 14%, respectively) (P < 0.05).When an LMA is used during desflurane anesthesia in children, fewer airway events occur when it is removed when the child is awake. Although the time to discharge from recovery was not delayed and no child required overnight admission, caution should be exercised when using an LMA in children who are anesthetized with desflurane.

Abstract

Pulmonary arterial hypertension (PAH) is associated with significant perioperative risk for major complications in children, including pulmonary hypertensive crisis and cardiac arrest. Uncertainty remains about the safety of ketamine anesthesia in this patient population.Retrospectively review the medical records of children with PAH to ascertain the nature and frequency of peri-procedural complications and to determine whether ketamine administration was associated with peri-procedural complications.Children with PAH (mean pulmonary artery pressure > or =25 mmHg and pulmonary vascular resistance index > or =3 Wood units) who underwent general anesthesia for procedures during a 6-year period (2002-2008) were enrolled. Details about the patient, PAH, procedure, anesthetic and postprocedural course were noted, including adverse events during or within 48 h of the procedure. Complication rates were reported per procedure. Association between ketamine and peri-procedural complications was tested.Sixty-eight children (median age 7.3 year, median weight 22 kg) underwent 192 procedures. Severity of PAH was mild (23%), moderate (37%), and severe (40%). Procedures undertaken were major surgery (n = 20), minor surgery (n = 27), cardiac catheterization (n = 128) and nonsurgical procedures (n = 17). Ketamine was administered during 149 procedures. Twenty minor and nine major complications were noted. Incidence of cardiac arrest was 0.78% for cardiac catheterization procedures, 10% for major surgical procedures and 1.6% for all procedures. There was no procedure-related mortality. Ketamine administration was not associated with increased complications.Ketamine appears to be a safe anesthetic option for children with PAH. We report rates for cardiopulmonary resuscitation and mortality that are more favorable than those previously reported.

Abstract

Although remifentanil has been used to induce hypotension during surgery in infants, no pharmacokinetic-pharmacodynamic (PKPD) model exists for its quantitative analysis. Our aim was to determine the quantitative relationship between whole blood remifentanil concentration and its hypotensive effect during surgery in infants.We studied seven infants (age 0.3-1 year) who underwent cranioplasty surgery and received remifentanil delivered by a computer-controlled infusion pump during the maintenance of anesthesia. Arterial blood samples to determine remifentanil concentration and mean arterial blood pressure (MAP) measurements were collected. A simultaneous PKPD mixed-effects model was built in NONMEM.A total of 77 remifentanil concentrations and 185 MAP measurements were collected. Remifentanil pharmacokinetics was described with a two-compartment model, parameter estimates were 2.99 l x min(-1) x 70 kg(-1) for clearance and 16.23 l x 70 kg(-1) for steady state volume of distribution. Mean baseline MAP was 69.7 mmHg and was decreased as per clinical requirements. A sigmoidal E(max) model driven by an effect compartment described the decrease in MAP, with an estimated concentration to decrease MAP by half (EC(50)) being 17.1 ng x ml(-1).Remifentanil is effective in causing hypotension. The final model predicts that a steady state remifentanil concentration of 14 ng.ml(-1) would typically achieve a 30% decrease in MAP.

Abstract

Children undergoing laryngotracheal reconstruction (LTR) may remain electively intubated in the pediatric intensive care unit (PICU) for several days following surgery to facilitate wound healing. These patients require sedation and analgesia with or without neuromuscular blockade in order to prevent excessive head and neck movement with resultant tension on the tracheal anastomosis. Achieving this level of immobility features in caring for these children.The aims of this article are to describe a variety of commonly used sedation and analgesic agents and to provide guidance as to their optimal use following LTR.

Abstract

Propofol is a sedative-hypnotic drug commonly used to anesthetize children undergoing esophagogastroduodenoscopy (EGD). Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist that has been utilized in combination with propofol to provide anesthesia. There is currently no information regarding the effect of intravenous dexmedetomidine on the propofol plasma concentration-response relationship during EGD in children. This study aimed to investigate the pharmacodynamic interaction of propofol and dexmedetomidine when used in combination for children undergoing EGD.A total of 24 children undergoing EGD, ages 3-10 years, were enrolled in this study. Twelve children received dexmedetomidine 1 microg x kg(-1) given over 10 min as well as a continuous infusion of propofol delivered by a computer-assisted target-controlled infusion (TCI) system with target plasma concentrations ranging from 2.8 to 4.0 microg x ml(-1) (DEX group). Another group of 12 children undergoing EGD also received propofol administered by TCI targeting comparable plasma concentrations without dexmedetomidine (control group). We used logistic regression to predict plasma propofol concentrations at which 50% of the patients exhibited minimal response to stimuli (EC50 for anesthesia).The EC50 +/- SE values in the control and DEX groups were 3.7 +/- 0.4 microg x ml(-1) and 3.5 +/- 0.2 microg x ml(-1), respectively. There was no significant shift in the propofol concentration-response curve in the presence of dexmedetomidine.The EC50 of propofol required to produce adequate anesthesia for EGD in children was unaffected by a concomitant infusion of dexmedetomidine 1 microg x kg(-1) given over 10 min.

Abstract

The aim of this study was to provide a model-based analysis of the pharmacokinetics of remifentanil in infants and children undergoing cardiac surgery with cardiopulmonary bypass (CPB).We studied nine patients aged 0.5 to 4 years who received a continuous remifentanil infusion via a computer-controlled infusion pump during cardiac surgery with mildly hypothermic CPB were studied. Arterial blood samples taken prior to, during and after CPB were analyzed for remifentanil concentrations using a validated gas-chromatographic mass-spectrophotometric assay. We used population mixed-effects modeling to characterize remifentanil pharmacokinetics. The final model was evaluated by its predictive performance.The pharmacokinetics of remifentanil was described by a 1-compartment model with adjustments for CPB. Population mean parameter estimates were 1.41 L for volume of distribution (V) and 0.244 L/min for clearance. V was increased during CPB and post-CPB to 2.41 times the pre-CPB value. The median prediction error and the median of individual median absolute prediction error were 2.44% and 21.6%, respectively.Remifentanil dosage adjustments are required during and after CPB due to marked changes in the V of the drug. Simulations indicate that a targeted blood concentration of 14 ng/mL is achieved and maintained in 50% of typical patients by administration of an initial dose of 18 mug remifentanil followed by an infusion of 3.7 mug/min before, during and post-CPB, supplemented with a bolus dose of 25 mug given at the start of CPB.

Abstract

Deep levels of sedation and analgesia are needed in the majority of children who require prolonged tracheal intubation after laryngotracheal reconstruction (LTR). Drug doses may be determined most appropriately using validated scoring tools for sedation and analgesia; these scales continue to evolve and are used with increasing regularity in the pediatric intensive care unit (PICU). In this presentation, the validated scoring tools used to assess sedation and analgesia are reviewed, and specific agents used to manage sedation, analgesia, and neuromuscular blockade in the PICU after LTR are discussed.

Abstract

Fenoldopam mesylate, a selective dopamine1-receptor agonist, is used by intravenous infusion to treat hypertension in adults. Fenoldopam is not approved by the FDA for use in children; reports describing its use in pediatrics are limited. In a multi-institutional, placebo controlled, double-blind, multi-dose trial we determined the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and side-effect profile of fenoldopam in children.Seventy seven (77) children from 3 weeks to 12 years of age scheduled for surgery in which deliberate hypotension would be induced were enrolled. Patients were randomly assigned to one of five, blinded treatment groups (placebo or fenoldopam 0.05, 0.2, 0.8, or 3.2 mcg/kg/min iv) for a 30-minute interval after stabilization of anesthesia and placement of vascular catheters. Following the 30-minute blinded interval, investigators adjusted the fenoldopam dose to achieve a target mean arterial pressure in the open-label period until deliberate hypotension was no longer indicated (e.g., muscle-layer closure). Mean arterial pressure and heart rate were continuously monitored and were the primary endpoints.Seventy-six children completed the trial. Fenoldopam at doses of 0.8 and 3.2 mcg/kg/min significantly reduced blood pressure (p < 0.05) during the blinded interval, and doses of 1.0-1.2 mcg/kg/min resulted in continued control of blood pressure during the open-label interval. Doses greater than 1.2 mcg/kg/min during the open-label period resulted in increasing heart rate without additional reduction in blood pressure. Fenoldopam was well-tolerated; side effects occurred in a minority of patients. The PK/PD relationship of fenoldopam in children was determined.Fenoldopam is a rapid-acting, effective agent for intravenous control of blood pressure in children. The effective dose range is significantly higher in children undergoing anesthesia and surgery (0.8-1.2 mcg/kg/min) than as labeled for adults (0.05-0.3 mcg/kg/min). The PK and side-effect profiles for children and adults are similar.

Abstract

Dexmedetomidine (DEX) is an alpha2-adrenergic agonist that is approved by the Food and Drug Administration for short-term (<24 h) sedation in adults. It is not approved for use in children. Nevertheless, the use of DEX for sedation and anesthesia in infants and children appears to be increasing. There are some concerns regarding the hemodynamic effects of the drug, including bradycardia, hypertension, and hypotension. No data regarding the effects of DEX on the cardiac conduction system are available. We therefore aimed to characterize the effects of DEX on cardiac conduction in pediatric patients.Twelve children between the ages of 5 and 17 yr undergoing electrophysiology study and ablation of supraventricular accessory pathways had hemodynamic and cardiac electrophysiologic variables measured before and during administration of DEX (1 microg/kg IV over 10 min followed by a 10-min continuous infusion of 0.7 microg x kg(-1) x h(-1)).Heart rate decreased while arterial blood pressure increased significantly after DEX administration. Sinus node function was significantly affected, as evidenced by an increase in sinus cycle length and sinus node recovery time. Atrioventricular nodal function was also depressed, as evidenced by Wenckeback cycle length prolongation and prolongation of PR interval.DEX significantly depressed sinus and atrioventricular nodal function in pediatric patients. Heart rate decreased and arterial blood pressure increased during administration of DEX. The use of DEX may not be desirable during electrophysiology study and may be associated with adverse effects in patients at risk for bradycardia or atrioventricular nodal block.

Abstract

We report the use of dexmedetomidine for laryngoscopy, rigid bronchoscopy, and tracheal extubation in the operating room in two children who had undergone tracheal reconstruction 1 week previously. Dexmedetomidine in combination with propofol provided appropriately deep anesthesia during these brief but stimulating procedures without cardiovascular or respiratory depression.

Abstract

Pain in the newborn is complex, involving a variety of receptors and mechanisms within the developing nervous system. When pain is generated, a series of sequential neurobiologic changes occur within the central nervous system. If pain is prolonged or repetitive, the developing nervous system could be permanently modified, with altered processing at spinal and supraspinal levels. In addition, pain is associated with a number of adverse physiologic responses that include alterations in circulatory (tachycardia, hypertension, vasoconstriction), metabolic (increased catabolism), immunologic (impaired immune response), and hemostatic (platelet activation) systems. This "stress response" associated with cardiac surgery in neonates could be profound and is associated with increased morbidity and mortality. Neonates undergoing cardiac operations are exposed to extensive tissue damage related to surgery and additional painful stimulation related to endotracheal and thoracostomy tubes that may remain in place for variable periods of time following surgery. In addition, postoperatively neonates endure repeated procedural pain from suctioning of endotracheal tubes, placement of vascular catheters, and manipulation of wounds (eg, sternal closure) and dressings. The treatment and/or prevention of pain are widely considered necessary for humanitarian and physiologic reasons. Improved clinical and developmental outcomes underscore the importance of providing adequate analgesia for newborns who undergo major surgery, mechanical ventilation, and related procedures in the intensive care unit. This article reviews published information regarding opioid administration and associated issues of tolerance and abstinence syndromes (withdrawal) in neonates with an emphasis on those having undergone cardiac surgery.

Abstract

This prospective study compared clinical outcomes after heart surgery between three groups of infants with congenital heart disease. One group received dilutional conventional ultrafiltration (group D), another received modified ultrafiltration (group M), and a third group received both dilutional conventional and modified ultrafiltration (group B). We hypothesized that group B patients would have the best clinical outcome.Children younger than 1 year undergoing heart surgery for biventricular repair by the same surgeon were randomly allocated to one of the three study groups. Patient management was standardized, and intensive care staff were blinded to group allocation. Primary outcome measure was duration of postoperative mechanical ventilation. Other outcome measures recorded included total blood products transfused, duration of chest tube in situ, chest tube output, and stays in intensive care and in the hospital.Sixty infants completed study protocol. Mean age and weight were as follows: group D (n = 19), 61 days, 4.3 kg; group M (n = 20), 64 days, 4.5 kg; and group B (n = 21), 86 days, 4.4 kg. Preoperative and intraoperative characteristics were similar between groups. Ultrafiltrate volumes obtained were 196 +/- 93 mL/kg in group D, 105 +/- 33 mL/kg in group M, and 261 +/- 113 mL/kg in group B. There were no significant differences between groups for any outcome variable. Technical difficulties prevented completion of modified ultrafiltration in 2 of 41 infants.There was no clinical advantage in combining conventional and modified ultrafiltration. Because clinical outcomes were similar across groups, relative risks of the ultrafiltration strategies may influence choice.

Abstract

To describe lung isolation and the selective application of continuous positive airway pressure using an endobronchial blocker in a patient with sickle cell disease and unilateral necrotizing Clostridium perfringens pneumonia.Case report.Pediatric intensive care unit.A 12-yr-old male with sickle cell disease developed persistent necrotizing pneumonia of the left lung following exchange transfusion for acute chest syndrome and hyper-hemolytic syndrome.An endobronchial blocker was placed into the left main stem bronchus for lung isolation and application of continuous positive airway pressure to the left lung for 48 hrs.After 14 days of persistent atelectasis of the left lung despite thorascopic decortication and multiple bronchoscopies, our patient had substantial lung aeration within 48 hrs of continuous positive airway pressure applied via the endobronchial blocker. Lung resection was avoided and the patient was successfully extubated 2 days after removal of the blocker.This case report demonstrates a therapeutic application of prolonged lung isolation and differential ventilation in a patient with an airway too small for commercially available double-lumen endotracheal tubes. The apparent success of this intervention suggests the feasibility of selective ventilation in pediatric patients and highlights a novel application of the bronchial blocker.

Abstract

Estimating appropriate tracheal tube (TT) depth following tracheal intubation in infants and children presents a challenge to anesthesia practitioners. We evaluated three methods commonly used by anesthesiologists to determine which one most reliably results in appropriate positioning.After IRB approval, 60 infants and children scheduled for fluoroscopic procedures requiring general anesthesia were enrolled. Patients were randomly assigned to one of three groups: (1) deliberate mainstem intubation with subsequent withdrawal of the TT 2 cm above the carina ('mainstem' method); (2) alignment of the double black line marker near the TT tip at the vocal cords ('marker' method); or (3) placement of the TT at a depth determined by the formula: TT depth (cm) = 3 x TT size (mmID) ('formula' method). TT tip position was determined to be 'appropriate' if located between the sternoclavicular junction (SCJ) and 0.5 cm above the carina as determined by fluoroscopy. Risk ratios were calculated, and data were analysed by the chi-square test accepting statistical significance at P < 0.05.The mainstem method was associated with the highest rate of appropriate TT placement (73%) compared with both the marker method (53%, P = 0.03, RR = 1.56) and the formula method (42%, P = 0.006, RR = 2.016). There was no difference between the marker and formula methods overall (P = 0.2, RR = 1.27). Analysis of age-stratified data demonstrated higher success with the marker method compared with the formula method for patients 3-12 months (P = 0.0056, RR = 4.0).Deliberate mainstem intubation most reliably results in appropriate TT depth in infants and children.

Abstract

Dexmedetomidine is a centrally acting alpha-2 adrenergic agonist that is currently approved by the US Food and Drug Administration for short-term use (< or = 24 h) to provide sedation in adults in the ICU. This drug has been shown to be efficacious in adult medical and surgical patients in providing sedation, anxiolysis, and analgesia. Dexmedetomidine has been associated with rapid onset and offset, hemodynamic stability, and a natural, sleep-like state in mechanically ventilated adults. To date, there are few publications of the use of this drug in children, and prolonged infusion has not been described. We report our use of dexmedetomidine in a child during a 4-day period of mechanical ventilation following tracheal reconstruction for subglottic stenosis.

Abstract

The aim of this prospective, randomized, controlled clinical trial was to define the opioid analgesic requirement after a remifentanil (REMI)-based anesthetic with spinal anesthetic blockade (SAB+REMI) or without (REMI) spinal blockade for open-heart surgery in children. We enrolled 45 patients who were candidates for tracheal extubation in the operating room after cardiac surgery. Exclusion criteria included age <3 mo and >6 yr, pulmonary hypertension, congestive heart failure, contraindication to SAB, and failure to obtain informed consent. All patients had an inhaled induction with sevoflurane and maintenance of anesthesia with REMI and isoflurane (0.3% end-tidal). In addition, patients assigned to the SAB+REMI group received SAB with tetracaine (0.5-2.0 mg/kg) and morphine (7 mug/kg). After tracheal extubation in the operating room, patients received fentanyl 0.3 mug/kg IV every 10 min by patient-controlled analgesia for pain score = 4. Pain scores and fentanyl doses were recorded every hour for 24 h or until the patient was ready for discharge from the intensive care unit. Patients in the SAB+REMI group had significantly lower pain scores (P = 0.046 for the first 8 h; P =0.05 for 24 h) and received less IV fentanyl (P = 0.003 for the first 8 h; P = 0.004 for 24 h) than those in the REMI group. There were no intergroup differences in adverse effects, including hypotension, bradycardia, highest PaCO(2), lowest pH, episodes of oxygen desaturation, pruritus, and vomiting.

Abstract

Surgical interventions, including video-assisted thoracoscopic surgeries, are increasingly being performed in the neonatal and pediatric populations. Thoracic anesthesia in infants and children poses special challenges for the anesthesiologist. These include assessment of the patient's clinical condition, obtaining and maintaining single lung ventilation, and maintaining adequate ventilation and oxygenation while the surgery is in progress.This review will outline the anesthetic management of infants and children undergoing thoracic surgery, including preoperative assessment, and anesthetic induction and maintenance. The physiology and methods of single lung ventilation will be reviewed, including the use of bronchial blockers, Univent tubes and double-lumen tubes. Special considerations for video-assisted thoracoscopic surgery, pectus repair and mediastinal masses will be discussed.These techniques will provide the anesthesiologist with a number of strategies for assessing the pediatric thoracic patient and for managing pediatric single lung ventilation.

Abstract

Pain management after thoracic surgery in children presents the challenge of providing adequate analgesia without excessive sedation, and maintaining adequate respiratory function in the face of compromise resulting from existing pathology, surgical trauma, single-lung ventilation and postoperative ventilation-perfusion abnormalities. In the pediatric population, pain assessment and reporting present additional challenges. The number and complexity of surgical procedures, including video-assisted thoracoscopic procedures, is increasing in the pediatric population. There is a need to explore pain management for these types of patients.There are effective and safe strategies whereby analgesia can be provided to this pediatric population. This review will outline the progress that has been made in this field, including the use of regional techniques. The routine use of caudal catheters in neonates and infants for thoracic surgical procedures and the use of electrical guidance of epidural catheters, the 'Tsui' technique, are reviewed.These techniques, applied within a comprehensive pain management strategy, can be extremely beneficial in the care of the pediatric thoracic patient.

Abstract

Propofol is commonly used to anesthetize children undergoing esophagogastroduodenoscopy. Opioids are often used in combination with propofol to provide total intravenous anesthesia. Because both propofol and remifentanil are associated with rapid onset and offset, the combination of these two drugs may be particularly useful for procedures of short duration, including esophagogastroduodenoscopy. The authors previously demonstrated that the median effective concentration (C50) of propofol during esophagogastroduodenoscopy in children is 3.55 microg/ml. The purpose of this study was to describe the pharmacodynamic interaction of remifentanil and propofol when used in combination for esophagogastroduodenoscopy in pediatric patients.The authors studied 32 children aged between 3 and 10 yr who were scheduled to undergo esophagogastroduodenoscopy. Propofol was administered via a target-controlled infusion system using the STANPUMP software based on a pediatric pharmacokinetic model. Remifentanil was administered as a constant rate infusion of 25, 50, and 100 ng.kg(-1).min(-1) to each of three study groups, respectively. A sigmoid Emax model was developed to describe the interaction of remifentanil and propofol.There was a positive interaction between remifentanil and propofol when used in combination. The concentration of propofol alone associated with 50% probability of no response was 3.7 microg/ml (SE, 0.4 microg/ml), and this was decreased to 2.8 microg/ml (SE, 0.1 microg/ml) when used in combination with remifentanil.A remifentanil infusion of 25 ng.kg(-1).min(-1) reduces the concentration of propofol required for adequate anesthesia for esophagogastroduodenoscopy from 3.7 to 2.8 microg/ml. Increasing the remifentanil infusion yields minimal additional decrease in propofol concentration and may increase the risk of side effects.

Anaesthetic management for the child with a mediastinal mass4th International Symposium on the Pediatric AirwayHammer, G. B.WILEY-BLACKWELL PUBLISHING, INC.2004: 95–97

Abstract

Administering anaesthesia to a child with an anterior mediastinal mass may lead to respiratory or circulatory collapse, even in those without symptoms. Institutions should have algorithms to manage children with mediastinal masses. Preoperative evaluations should include computed tomography, echocardiography and flow-volume studies. Anaesthesia may be induced with inhalation agents and maintained with spontaneous respiration via facemask or laryngeal mask airway. Alternatively, positive-pressure ventilation may be used, including tracheal intubation without muscle relaxants. Rigid bronchoscopy may be life-saving in the event of tracheal or bronchial collapse under anaesthesia.

Abstract

During the past decade, the use of video-assisted thoracoscopic surgery (VATS) has dramatically increased in children as well as adults. Although VATS can be performed while both lungs are being ventilated, single-lung ventilation (SLV) is desirable during VATS. In addition, anaesthesiologists are performing (and paediatric surgeons are requesting) SLV more frequently for open thoracotomies in infants and children.

Abstract

The anesthesiologist caring for infants and children undergoing thoracic surgery faces many challenges. An understanding of the primary underlying lesion as well as associated anomalies that may impact perioperative management is paramount. A working knowledge of respiratory physiology and anatomy in infants and children is required for the planning and execution of appropriate intraoperative care. Familiarity with a variety of techniques for SLV suited to the patient's size will allow maximal surgical exposure while minimizing trauma to the lungs and airways. Finally, use of regional anesthetic techniques, including epidural anesthesia and analgesia, facilitates optimal postoperative pain control and pulmonary function.

Abstract

As video-assisted thoracoscopic surgery has become more common in paediatric patients, the use of single lung ventilation in children has also increased. Single lung ventilation in young children is performed by either advancing a tracheal tube into the mainstem bronchus opposite the side of surgery or by positioning a bronchial blocker into the mainstem bronchus on the operative side. Techniques for placing a variety of bronchial blockers outside the tracheal tube have been described. We describe a technique for placement of a new bronchial blocker through an indwelling tracheal tube using a multiport adaptor and a fibreoptic bronchoscope.

Abstract

Tracheal extubation of patients with a difficult airway represents a challenge to anaesthesiologists and intensive care physicians. While a variety of techniques designed to maintain access to the airway in case of the need for tracheal reintubation have been described in adults, no reports have been published in infants and young children. We describe an approach to this issue in a young child with severe micrognathia.

Abstract

Propofol is commonly used to provide anaesthesia for children undergoing oesophagogastroduodenoscopy (OGD). Despite this, the plasma concentration-response relationships for propofol used in this setting have not been established.In order to determine the EC50 of propofol during OGD, we studied 12 children aged 3-10 years. No premedication was given. Propofol was administered via a target-controlled infusion system using the STANPUMP software based on a paediatric pharmacokinetic model. The 'up-and-down' method described by Dixon was used to determine the EC50. Accordingly, the target plasma propofol concentration for each patient, beginning with the second subject, was determined by the response of the previous patient. A patient was considered a 'responder' if there was minimal movement and the heart rate (HR) and blood pressure (BP) remained < or = 120% of baseline during the procedure. Patients who moved excessively, i.e. requiring more than gentle restraint, or who manifest HR and BP >120% of baseline, were considered 'nonresponders'.The EC50 of propofol during OGD was 3.55 microg.ml(-1) in this study.The plasma propofol concentration associated with adequate anaesthesia for OGD in 50% of unpremedicated children is 3.55 microg.ml(-1). This concentration is higher than that required for OGD in adult patients.

Abstract

The use of regional anesthesia in combination with general anesthesia for children undergoing cardiac surgery is receiving increasing attention from clinicians. The addition of regional anesthesia may improve clinical outcomes and decrease costs as a result of the reduced need for postoperative mechanical ventilation. The goal of this retrospective chart review was to evaluate whether spinal anesthesia (SAB) or epidural anesthesia (EPID) in combination with general anesthesia was associated with circulatory stability, satisfactory postoperative sedation/analgesia, and a low incidence of adverse effects. The medical records of 50 consecutive children having open heart surgery with SAB or EPID and general anesthesia between September 1996 and December 1997 were reviewed. We found no significant differences in the incidence of clinically significant changes in vital signs, oxygen desaturation, hypercarbia, or vomiting. Patients in the SAB group received significantly more sedative/analgesic interventions than those in the EPID group.

Abstract

Tracheal intubation of a child with trismus pseudocamptodactyly (Hecht) syndrome is described. This disorder is characterized by progressive trismus and the need for repeated surgeries. Children intubated orally on a prior occasion may require an alternative approach subsequently due to progressive inability to open the mouth. An antegrade fiberoptic-guided nasotracheal technique initially was chosen due to extremely limited mouth opening. After this approach was unsuccessful, a retrograde guidewire-assisted fiberoptic intubation was performed. The manifestations of Hecht syndrome, as well as both techniques for tracheal intubation employed, are reviewed.

Abstract

A Univent bronchial blocker tube was used in a ten-year-old patient undergoing videothoracoscopy. Paediatric Univent tubes offer an alternative to balloon-tipped catheters for providing single-lung ventilation (SLV) in children too small for adult size double-lumen tubes.

Abstract

Ten consecutive patients with failure of urinary bladder augmentation (UBA) performed either prior to or after reaching end-stage renal disease (ESRD) were studied. Seven patients developed increased hydroureteronephrosis, infectious complications, and advanced to ESRD after UBA. The mean time to development of ESRD in patients who had UBA performed with moderate chronic renal failure (CRF) was 1.8 years. The UBAs in all seven patients were taken down prior to transplantation. Subsequently, five of these UBA-takedown patients have received kidney grafts and all have stable, good renal function. Three patients had their UBA performed after they reached ESRD, in preparation for renal transplantation. All three of these patients experienced recurrent urosepsis following transplantation, resulting in death in one patient and loss of graft in another. The third patient will undergo takedown of the UBA. This study suggests that UBA may possibly not be the best option for patients with moderate CRF and those awaiting transplantation.

Abstract

Nationally, results of renal transplantation in children, particularly in small children, are inferior to those obtained in adults.To determine factors important for success in renal transplantation in children.Results of 108 consecutive renal transplantations performed in patients aged 7 months to 18 years were reviewed and compared with those reported by the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), the national registry.One-, 2-, and 3-year graft survival rates (+/-SE) were 99% +/- 1%, 95% +/- 3%, and 93% +/- 4%, respectively, for living donor grafts and 97% +/- 3%, 92% +/- 6%, and 92% +/- 6%, respectively, for cadaver grafts. Incidence of acute rejection was half that reported by NAPRTCS. There were no graft losses for technical reasons (19% in NAPRTCS). Twelve percent of patients were younger than 2 years (6% in NAPRTCS); 17% were 2 to 5 years old (16% in NAPRTCS). Most small children received an adult-sized kidney. Ninety-three percent of recipients weighing 15 kg or less received postoperative mechanical ventilation assistance to optimize fluid resuscitation and perfusion of adult-sized kidneys. Structural abnormalities of the urinary tract were present in 53.7% of the patients (48.5% in NAPRTCS; adults, 5.3%). Nephroureterectomy was required in 38 children; in 27 (71%) of them, it was performed at the time of transplant surgery.Excellent results can be obtained in pediatric renal transplantation by strict adherence to surgical detail, tight immunosuppressive management, aggressive fluid management in the small child, and careful integration of urologic and transplant surgery.

Abstract

Children who experience acute liver failure following liver transplantation will have multiple organ failure and a high rate of mortality unless emergency retransplantation can be performed. Transplant hepatectomy with portocaval shunting has been described as a bridge to transplantation in the most severe cases, as well as in patients with fulminant hepatic failure at high risk for mortality who have not undergone liver transplantation. Patients with multiple organ failure who have undergone hepatectomy require renal replacement therapy. Continuous hemofiltration may be used in patients with fulminant hepatic failure to facilitate fluid removal and circulatory and metabolic balance. We used continuous venovenous hemofiltration with dialysis following hepatectomy with portocaval shunting in a patient who remained anhepatic for 66 hr in order to achieve circulatory and metabolic homeostasis as well as stable neurologic function prior to successful retransplantation.

Abstract

Trimethaphan camsylate is a potent antihypertensive drug used to induce systemic arterial hypotension in patients undergoing major surgery and to treat severe systemic hypertension. The pharmacokinetics and pharmacodynamics of trimethaphan administered in the usual clinical dosages have been previously reported. The effects of trimethaphan when administered in very high doses of 500-1000 times the usual dose have not been reported.A case is presented of an infant with severe hypertension who inadvertently received such an overdose of trimethaphan.